Evaluating naloxegol for the treatment of opioid-induced constipation

ABSTRACT

Introduction

Due to the increased use of opioids for pain and their abuse globally, the rate of restrictive side effects is elevating. Opioid-induced constipation (OIC) is probably the most widespread, underdiagnosed, and yet common adverse effect. Naloxegol, as an opioid antagonist, is associated with beneficial impacts in OIC. Indeed, blocking mu (μ)-opioid receptors in the gastrointestinal tract (GI) may lead to neutralization of the GI adverse events of opioids.

Areas covered

This review is based on a PubMed and Clinicaltrials.gov search for studies undertaken over the past 20 years (2000–2020) using the following keywords: Movantik®, Moventig®, Naloxegol, Opioids, Opioid-induced constipation and Opioid antagonists.

Expert opinion

Similar to the management of functional constipation, non-pharmacological therapies are applied as the first step of the procedure. However, in most cases, laxative therpaies with or without stool softeners, which may not result in satisfactory relief are applied. In these instances, administration of prokinetic agents is recommended. Furthermore, studies have shown that the best second-line therapy option is a peripherally acting μ-opioid receptor antagonist (PAMORA), which antagonizes GI adverse events.

KEYWORDS:

• Movantik®
• Moventig®
• Mu (μ) opioid receptor
• naloxegol
• opioid antagonists
• opioid-induced constipation
• constipation
• PAMORA
• expert opinion

Article highlights

• OIC is the most widespread and restrictive adverse effect of administration of opioids which significantly deteriorates the QOL of the patient.

• Non-pharmacological management and laxative therapy in the treatment of OIC do not result in significant and satisfactory improvements. Therefore, administration of prokinetics, prosecretory agents and PAMORAs (e.g., naloxegol) are recommended.

• Naloxegol is a competitive antagonist of δ, κ, and μ opioid receptors with a higher binding affinity to κ, and μ receptors.

• Naloxegol, PEGylated derivative of naloxone, at the dose of 12.5 to 25 mg daily showed beneficial effects in the management of OIC.

• Due to the limited passage of naloxegol through BBB, this drug antagonizes peripheral side effects of opioids such as GI complications. Furthermore, the prevalence of cardiovascular adverse events (e.g., MI and QT prolongation) of naloxegol is significantly less than other PAMORAs such as alvimopan.

• Nausea, vomiting, diarrhea, abdominal pain and bowel obstruction are the most common adverse effect of naloxegol.

• Lack of life-threatening adverse effects, absence of withdrawal complications and deficiency of risk of abuse or dependency are counted as superiorities of naloxegol among other PAMORAs.

Box 1. Drug summary.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded